Toxicity and human health risk of hair dyes.

Hair dyes and their ingredients have moderate to low acute toxicity. Human poisoning accidents are rare and have only been reported following oral ingestion. Contact sensitisation to hair dyes has been a safety issue, mainly as a consequence of unprotected professional exposure. Although the use of hair dyes has dramatically increased in industrialised countries during the last decades, the prevalence of sensitisation to hair dyes in the general and professional populations has stabilised or declined. In vitro genotoxicity tests on hair dye ingredients frequently had positive results, although their correlation with in vivo carcinogenicity for the chemical class of oxidative hair dye ingredients (aromatic amines) is uncertain. Positive in vivo genotoxicity results on hair dyes are rare. Studies in man found no evidence of genotoxic effects of hair dyes or their ingredients. On the basis of mechanistic studies, some in vivo positive hair dye ingredients (p-aminophenol, Lawsone) have been shown to pose no or negligible risk to human health. Although a recent case-control epidemiology study suggested an association of hair dye use and bladder cancer, a number of other studies, including prospective investigations on large populations, found no or negative correlations for bladder or other cancers. Although in vivo topical carcinogenicity studies on hair dye ingredients or commercial formulations yielded no evidence for systemic toxicity or carcinogenicity, oral carcinogenicity studies on hair dye ingredients at oral doses up to the maximum tolerated dose (MTD) suggested that some ingredients are carcinogenic in rodents. Human systemic exposure to various (14)C-labelled oxidative hair dyes under conditions of use was below 1.0% of the amount applied. Conservative risk assessments suggested no or negligible cancer risk, including for ingredients that were found to be positive in oral carcinogenicity studies. The results of reproductive toxicity studies and epidemiological investigations suggested that hair dyes and their ingredients pose no risk of adverse reproductive effects. In conclusion, the weight of evidence suggests that consumer or professional exposure to hair dyes poses no carcinogenic or other human health risks.

Human systemic exposure to a [14C]-para-phenylenediamine-containing oxidative hair dye and correlation with in vitro percutaneous absorption in human or pig skin.

We investigated the absorption of a commercial [14C]-PPD-containing oxidative dark-shade hair dye in human volunteers as well as in vitro using human or pig ear skin. The hair of eight male volunteers was cut to a standard length, dyed, washed, dried, clipped and collected. Hair, washing water, materials used in the study and a 24-h scalp wash were collected for determination of radioactivity. Blood, urine and faeces were analysed up to 120 h after hair dyeing. An identical [14C]-PPD-containing hair dye formulation was applied in vitro for 0.5 h to human and pig ear skin, and radioactivity was determined in skin compartments after 24 h. In humans, the recovery rate was 95.7+/-1.5% of the applied radioactivity. Washing water, cut hair, gloves, paper towels, caps or scalp wash contained a total of 95.16+/-1.46% of the applied [14C]. Absorbed radioactivity amounted to 0.50+/-0.24% in the urine and 0.04+/-0.04% in the faeces, corresponding to a mean of 7.0+/-3.4 mg [14C]-PPD-equivalents absorbed. Within 24 h after application, most of the radioactivity was eliminated. The Cmax of [14C]-PPD-equivalents in the plasma was 0.087 microgeq/ml, the Tmax was approximately 2 h, and the mean the AUC(0-12h) was 0.67 microgeq h/ml. In vitro tests in human or pig skin found total absorbed amounts of 2.4+/-1.6% (10.6+/-6.7 microgeq/cm2) or 3.4+/-1.7% (14.6+/-6.9 microgeq/cm2), respectively. Percentage-based in vitro results were considerably higher than corresponding in vivo data, whereas, in units of microg/cm2, they corresponded to a total absorbed amount of 7.40 or 10.22 mgeq for human or pig skin, respectively. All results suggested that hair dyeing with oxidative hair dyes produces minimal systemic exposure that is unlikely to pose a risk to human health.

Comparison of cutaneous bioavailability of cosmetic preparations containing caffeine or alpha-tocopherol applied on human skin models or human skin ex vivo at finite doses.

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine's and alpha-tocopherol's cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm and Episkin. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and alpha-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.